Compositions and Methods for Treating Dopamine Disorders
Compositions comprising clathrin nanoparticles and methods for treating dopamine-associated addictions, disorders, and neurodegenerative diseases using the same.
1 . A composition comprising:
(i) a dopamine active transporter (DAT) targeting agent comprising a dopamine re-uptake inhibitor (DRI) or an anti-DAT antibody; (ii) a neurotrophin; and (iii) a carrier that protects the composition against rapid elimination from the body of the living subject,
wherein the DAT targeting agent and neurotrophin are linked to a clathrin nanoparticle.
2 . The composition of claim 1 , wherein the DRI is selected from the group consisting of -Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone, Altropane (O-587), Amfonelic acid (WIN 25978), Amineptine, BTCP (GK-13), 3C-PEP, DBL-583, Difluoropine (O-620), GBR-12783, GBR-12935, GBR-13069, GBR-13098, GYKI-52895, Iometopane (β-CIT, RTI-55), Methylphenidate, Ethylphenidate, Modafinil, Armodafinil, RTI-229, Vanoxerine (GBR-12909), drafinil, Amantadine, Benztropine, Bupropion, Fluorenol, Ketamine, Medifoxamine, Metaphit, Rimcazole, Sertraline, St. John's Wort, Venlafaxine, Chaenomeles speciose, 3-Methoxyphencyclidine, 4-Methoxyphencyclidine, and Oroxylin A.
3 . The composition of claim 1 , wherein the neurotrophin comprises brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), neurotrophin-6 (NT-6), glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), persephin (PSPN), artemin (ARTN), ciliary neurotrophic factor (CNTF), or leukemia inhibitory factor (LIF).
4 . The composition of claim 1 , wherein the carrier is a biodegradable, biocompatible polymer.
5 . The composition of claim 4 , wherein the carrier comprises ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, or polylactic acid
6 . The composition of claim 1 , wherein the composition is prepared as a controlled release formulation.
7 . The composition of claim 6 , wherein the composition comprises an implant or a microencapsulated delivery system.
8 . The composition of claim 1 , wherein the DAT targeting agent and/or the neurotrophin is linked to the clathrin nanoparticle by conjugation.
9 . The composition of claim 8 , wherein the DAT targeting agent is conjugated to the clathrin nanoparticle via polyethylene glycol (PEG).
10 . The composition of claim 8 , wherein the neurotrophin is conjugated to the clathrin nanoparticle via PEG.
11 . A method for treating a human subject having or at risk for developing a dopamine disorder comprising administering to the human subject a therapeutically effective amount of the composition of claim 1 .
12 . The method of claim 11 , wherein the dopamine disorder is a neurodegenerative disease associated with loss of dopaminergic neurons.
13 . The method of claim 12 , wherein the neurodegenerative disease associated with loss of dopaminergic neurons is Parkinson's disease, Huntington's disease, Alzheimer's disease, or ALS.
14 . The method of claim 11 , wherein the dopamine disorder is ADHD, depression, or schizophrenia.
15 . The method of claim 11 , wherein the dopamine disorder is a dopamine-driven addiction.
16 . The method of claim 11 , wherein the composition is delivered intranasally or intravenously.